Chloramphenical, thiamphenicol and florfenicol are broad spectrum antibiotics known generically as “fenicols.” Florfenicol is a broad spectrum antibiotic with activity against many gram-negative and gram-positive bacteria. Florfenicol is useful for the prevention and treatment of bacterial infections due to susceptible pathogens in mammals, birds, reptiles, fish and shellfish. One of its primary uses is in the treatment of pneumonia and associated respiratory infections in cattle (often referred to generically as Bovine Respiratory Disease or BRD) caused by Mannhemia haemolytica, Pasteurella multocida and(or) Histophilus somni. It is also indicated in the treatment of infectious pododermatitis in cattle caused by Fusobacterium necrophorum and/or Prevotella melaninogenicus, swine respiratory disease caused by Pasteurella multocida, Actinobacillus pleuropneumoniae, Streptococcus suis, Salmonella cholerasuis and(or) Mycoplasma spp., colibacillosis in chickens caused by Escherichia coli, enteric septicemia in catfish caused by Edwardsiella ictaluri, and furunculosis in salmon caused by Aeromonas salmonicida. Other genera of bacteria that have exhibited susceptibility to florfenicol include Enterobacter, Klebsiella, Staphylococcus, Enterococcus, Bordetella, Proteus, and Shigella. In particular, chloramphenicol resistant strains of organisms such as K. pneumoniae, E. cloacae, S. typhus and E. coli are susceptible to florfenicol.
As shown below, florfenicol is a structural analog of thiamphenicol which, in turn, is a derivative of chloramphenicol, wherein the aromatic nitro group that has been implicated in chloramphenicol-induced, non-dose related irreversible aplastic anemia in humans is replaced with a methylsulfonyl group.

Florfenicol has a fluorine atom in place of the primary hydroxyl group of chloramphenicol and thiamphenicol. This renders florfenicol less susceptible to deactivation by bacteria containing the plasmid-encoded enzyme, chloramphenicol acetyl transferase (CAT), which acetylates the primary hydroxyl group of chloramphenicol and thiamphenicol. The acetylation prevents these antibiotics from binding to ribosomal subunits of susceptible bacteria. The binding of this class of antibiotic to ribosomal subunits is the primary (but not the sole) mechanism of action of chloramphenicol and thiamphenicol in inhibiting peptidyl transferase, which is responsible for the transfer of amino acids to growing peptide chains and subsequent protein formation, in bacteria.
Florfenicol is most often administered to a subject which can benefit from its advantages either orally, subcutaneously, or parenterally, the latter being primarily intramuscular or intravenous. Given the need for economical, single-dose treatment in the veterinary setting, there remains a need for new formulations of florfenicol at high concentrations.
In addition, there is also a need for a form of florfenicol that is capable of maintaining effective plasma antibiotic levels for prolonged periods of time, in order to achieve improved economies in administration, e.g., to more readily provide single dose treatment, particularly in a veterinary setting.
In an effort to extend the benefits of a single injection of florfenicol, the art has considered florfenicol ester derivatives as prodrugs. For example, Murthy et al., in published U.S. patent application No. 2005/0014828, have described esterified florfenicols such as florfenicol acetate, florfenicol propionate, florfenicol butyrate, florfenicol pentanoate, florfenicol hexanoate, florfenicol heptanoate, florfenicol octanoate, florfenicol nanoate, florfenicol decanoate, florfenicol undecanoate, florfenicol dodecanoate, and florfenicol phthalate, and the like.
Florfenicols with enhanced water solubility, and prodrug activity in the form of florfenicol phosphate esters are also described in co-owned published U.S. patent application No. 2005/0182031.
Nevertheless, there remains a longstanding need in the art for additional fenicols, with enhanced solubility in suitable carriers that can provide economical single dose treatment.
The citation of any reference herein should not be construed as an admission that such reference is available as “prior art” to the instant application.